PYY3–36 and Oxyntomodulin Can Be Additive in Their Effect on Food Intake in Overweight and Obese Humans

Field, Benjamin; Wren, Alison; Peters, V; Baynes, Kevin; Martin, Niamh; Patterson, Michael; Alsaraf, Sara; Amber, Vian; Wynne, Katie; Ghatei, Mohammad A.; Bloom, Stephen R.

doi:10.2337/db09-1859

Cited by 105 publications

(61 citation statements)

References 33 publications

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“…Vagal sparing during RYGBP resulted in and the long term (measured indirectly at three years) (86) postoperatively. Interestingly, the anorectic effects of oxyntomodulin are additive to those of PYY in obese humans (90), indicating a biologically plausible role for this L cell product in mediating the effects of RYGBP on feeding behavior. In contrast, CCK levels are not significantly altered after RYGBP (74,88).…”

Section: Insights From Animal Modelsmentioning

confidence: 99%

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Manning¹,

Pucci²,

Batterham³

2015

J. Clin. Invest.

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Section: Insights From Animal Modelsmentioning

confidence: 99%

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Manning¹,

Pucci²,

Batterham³

2015

J. Clin. Invest.

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“…Similarly, a pharmacologic formulation of PYY(3-36) failed because of side-effects (nausea and vomiting) [78]. Recently, PYY(3-36) was suggested for use as anti-obesity treatment in combination with oxyntomodulin [79]. This would allow augmented action on appetite suppression through additive effects of PYY(3-36) and oxyntomodulin.…”

Section: Peptide Yymentioning

confidence: 99%

Therapy for Obesity Based on Gastrointestinal Hormones

Christensen¹,

Knop²,

Vilsbøll³

2011

Rev Diabet Stud

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■ AbstractIt has long been known that peptide hormones from the gastrointestinal tract have significant impact on the regulation of nutrient metabolism. Among these hormones, incretins have been found to increase insulin secretion, and thus incretin-based therapies have emerged as new modalities for the treatment of type 2 diabetes. In contrast to other antidiabetic treatments, these agents have a positive outcome profile on body weight. Worldwide there are 500 million obese people, and 3 million are dying every year from obesityrelated diseases. Recently, incretin-based therapy was proposed for the treatment of obesity. Currently two different incretin therapies are widely used in the treatment of type 2 diabetes: 1) the GLP-1 receptor agonists which cause significant and sustained weight loss in overweight patients, and 2) dipeptidyl peptidase 4 (DPP-4) inhibitors being weight neutral. These findings have led to a greater interest in the physiology of intestinal peptides with potential weightreducing properties. This review discusses the effects of the incretin-based therapies in obesity, and provides an overview of intestinal peptides with promising effects as potential new treatments for obesity.

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“…Acute peripheral administration of PYY3-36 has been demonstrated to reduce food intake in both lean and obese animals and humans (Batterham et al, 2002, Pittner et al, 2004, Koegler et al, 2005, le Roux et al, 2006and Field et al, 2010. In diet-induced obese rodents, PYY3-36 has also been shown to promote lipid oxidation and/or reduce lipogenesis (Adams et al, 2006 andvan den Hoek et al, 2007), as well as to enhance insulin-mediated glucose disposal (van den Hoek et al, 2004, van den Hoek et al, 2007, Boey et al, 2006aand Boey et al, 2006b, further demonstrating the potential therapeutic value of PYY3-36 in the treatment of obesity and type-2 diabetes.…”

Section: Introductionmentioning

confidence: 97%

Adult-onset PYY overexpression in mice reduces food intake and increases lipogenic capacity

et al. 2012

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Peptide YY (PYY) is best known for its important role in appetite regulation, but recent pharmacological studies have suggested that PYY is also involved in regulating energy balance and glucose homeostasis. However, the mechanism behind the regulation of these parameters by PYY is less clear. Here, by utilising an inducible transgenic mouse model where PYY overexpression is induced in adult animals (PYYtg) and release of mature PYY peptides is controlled by endogenous machineries, we show that elevating PYY levels leads to reduced food intake after a 24-h fast. Furthermore, PYYtg mice, although not significantly different from WT with respect to body weight, adiposity, lean mass, physical activity or energy expenditure, exhibited a significantly increased respiratory exchange ratio (RER), indicating decreased lipid oxidation and/or increased lipogenesis. Importantly, PYYtg mice showed a 25% reduction in liver protein levels of phosphorylated acetyl-CoA carboxylase (pACC) in the absence of changes in total ACC levels compared to those of WT mice. Moreover, liver protein levels of AMP-activated kinase (AMPK) in PYYtg mice were 25% lower than those of WT mice, consistent with a reduced pACC in these mice. These data suggest that elevation of PYY levels as seen after a meal can increase lipogenic capacity, which is likely a key contributor to the increased RER seen in PYYtg mice. In addition, PYYtg mice exhibited comparable insulin tolerance and oral glucose tolerance to those of WT, but showed a trend towards decreased insulin levels in response to an oral glucose challenge, indicating that PYY could improve insulin action. Taken together, these findings demonstrate that under physiological conditions, PYY reduces food intake while enhancing lipogenic capacity and insulin action, likely contributing to fuel assimilation in the postprandial state.

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PYY3–36 and Oxyntomodulin Can Be Additive in Their Effect on Food Intake in Overweight and Obese Humans

Cited by 105 publications

References 33 publications

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Therapy for Obesity Based on Gastrointestinal Hormones

Adult-onset PYY overexpression in mice reduces food intake and increases lipogenic capacity

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